rs7077757

Variant names:

• chr10-110784897-C-T
• rs7077757
• NM_001134363.3:c.1527+8C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001134363.3(RBM20):​c.1527+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,444,144 control chromosomes in the GnomAD database, including 32,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3489 hom., cov: 32)
  • Exomes 𝑓: 0.21 (29496 hom.)
• Consequence: RBM20 NM_001134363.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001230
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.123
• Publications: 15 publications found

Genes affected

RBM20 (HGNC:27424): (RNA binding motif protein 20) This gene encodes a protein that binds RNA and regulates splicing. Mutations in this gene have been associated with familial dilated cardiomyopathy. [provided by RefSeq, Apr 2014]

RBM20 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dilated cardiomyopathy 1DD

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-110784897-C-T is Benign according to our data. Variant chr10-110784897-C-T is described in ClinVar as Benign. ClinVar VariationId is 43975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134363.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	NM_001134363.3	MANE Select	c.1527+8C>T		splice_region intron	N/A	NP_001127835.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	ENST00000369519.4	TSL:1 MANE Select	c.1527+8C>T		splice_region intron	N/A	ENSP00000358532.3
	RBM20	ENST00000961386.1		c.1557+8C>T		splice_region intron	N/A	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.1527+8C>T		splice_region intron	N/A	ENSP00000520684.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31898 AN: 151950 Hom.: 3479 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.192

GnomAD2 exomes AF: 0.185 AC: 25732 AN: 139300 AF XY: 0.180

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.0828

Gnomad FIN exome AF: 0.223

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.209 AC: 270142 AN: 1292076 Hom.: 29496 Cov.: 20 AF XY: 0.206 AC XY: 131831 AN XY: 640486

African (AFR) AF: 0.219 AC: 6290 AN: 28778

American (AMR) AF: 0.164 AC: 5117 AN: 31220

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4247 AN: 23984

East Asian (EAS) AF: 0.0695 AC: 2445 AN: 35174

South Asian (SAS) AF: 0.103 AC: 7553 AN: 73364

European-Finnish (FIN) AF: 0.226 AC: 11079 AN: 49092

Middle Eastern (MID) AF: 0.112 AC: 611 AN: 5458

European-Non Finnish (NFE) AF: 0.224 AC: 222087 AN: 990560

Other (OTH) AF: 0.197 AC: 10713 AN: 54446

GnomAD4 genome AF: 0.210 AC: 31939 AN: 152068 Hom.: 3489 Cov.: 32 AF XY: 0.207 AC XY: 15415 AN XY: 74350

African (AFR) AF: 0.221 AC: 9157 AN: 41438

American (AMR) AF: 0.186 AC: 2849 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3466

East Asian (EAS) AF: 0.0866 AC: 449 AN: 5182

South Asian (SAS) AF: 0.0995 AC: 479 AN: 4812

European-Finnish (FIN) AF: 0.221 AC: 2337 AN: 10576

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15470 AN: 67976

Other (OTH) AF: 0.194 AC: 411 AN: 2114

Alfa AF: 0.216 Hom.: 16182

Bravo AF: 0.207

Asia WGS AF: 0.119 AC: 416 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Dilated cardiomyopathy 1DD (2)
-	-	1	not provided (1)
-	-	1	Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.6
DANN	Benign	0.45
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7077757; hg19: chr10-112544655; COSMIC: COSV65707353;